Primary and secondary hyperalgesia

After a tissue injury, the area around the injury becomes hypersensitive and light touch can elicit pain. There are two aspects to the hyperalgesia: primary hyperalgesia is defined as the hypersensitive area at the site of the injury. It is due to an 'inflammatory soup' of endogenout algesic agents.

Secondary hyperalgesia develops in uninjured tissue surrounding the site of injury, and is thought to be a result of sensitization in the central nervous system, including the dorsal horn.

The diagram opposite indicates that mechanisms that increase synaptic strength within the dorsal horn may be responsible. Upregulation of the production of peptide neurotransmitters, changes in gene transcription in the cells of the dorsal horn and changes in the effects of descending contol pathways may all play a part in the responses.

The lower diagram opposite indicates that in hyperalgesic states there is a leftward shift in the stimulus response curve, indicating that pain is induced at lower stimulus intensities.

Allodynia is the mild pain that is present in response to light touch stimuli, and hyperalgesia is the hightened response to a painful stimulus.

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There are several types of voltage-gated sodium channels including several in sensory neurones. Two, NaV1.7 and NaV1.8, are coded by genes, SCN9A and SCN10A respectively. NaV1.7 is the normal voltage-gated sodium channel in nerves, and is sensitive to tetrodotoxin (TTX, a poison extracted from Puffer Fish, and used by them to paralyse their prey). NaV1.8 is a TTX-resistant voltage gated sodium channel which is present in C-fibre afferents in some experimental neuropathies, and in a significant percentage of humans with persistent chronic neuropathies.

NaV1.8 is known to be involved in hyperalgesia and allodynia in experimental investigations; studies of NaV1.8 knockout mice have shown that the channel is associated with inflammatory and neuropathic pain, and particularly with cold pain.

Biochemical, anatomical and physiological changes of lesioned primary afferent neurons following nerve lesion and the subsequent central changes.

(http://www.physiologie.uni-kiel.de/homepages_mitarbeiter/jaenig/neu/hompage.html)

This diagram show some of the changes that contribute to the development of chronic pain, and appear to be relevant to the neuropathic pain that occurs after nerve injury. See the secion of Phantom Limbs.